The present invention relates to an ion source, preferably an Electrospray ionisation ion source, a mass spectrometer, a method of ionising a sample and a method of mass spectrometry.
Electrospray Ionisation (“ESI”) has established itself as the most widely used ionisation technique for Liquid Chromatography/Mass Spectrometry (“LC/MS”) systems. Electrospray ionisation involves passing a liquid down an open tubular capillary which is maintained at a relatively high voltage with respect to an ion sampling orifice of an adjacent mass spectrometer. In the case of high liquid flow rates (e.g. 5-1000 μl/min) it is common to use a combination of a concentric flow of a high velocity nebulisation gas and a heated desolvation gas in order to aid the desolvation process.
Charged droplets are formed by the combined action of electrostatic and electrohydrodynamic forces at the capillary tip. The droplets then undergo desolvation until a point is reached where the increasing repulsive forces within the droplet exceed the surface tension. At this point of instability, termed the Rayleigh limit, the droplets undergo a fission process which results in the production of a number of smaller charged droplets commonly referred to as progeny droplets. The desolvation and, fission process can then proceed further so that second generation charged droplets are produced which are even smaller. A point is then reached where ions are released into the gas phase according to an ion evaporation or charge residue model.
Most theories concerning the mechanism of Electrospray ionisation predict that relatively high efficiency Electrospray ionisation can be achieved from highly charged small droplets having a high surface charge density. Gas phase ions are obtained from first or early generation progeny droplets that require only mild desolvation.
Nanospray ionisation, which is conducted at flow rates of 10-100 nl/min, is an example of a high efficiency Electrospray process wherein sub-micron, highly charged, first generation droplets are generated without the need for concentric nebulisation or desolvation gases. Nanospray ionisation from early generation droplets is also less susceptible to matrix suppression effects wherein co-eluting sample matrix components become concentrated during desolvation and compete with the analyte ions for the available charge.
Conversely, conventional Electrospray ionisation at relatively high flow rates (e.g. 100-1000 μl/min) is relatively inefficient since relatively large (>10 μm) droplets are created having a relatively low surface charge density. Relatively high desolvation temperatures are required in order to yield ions from later generation droplets and the process is more susceptible to matrix suppression effects.
Commercially available Electrospray ionisation ion sources for mass spectrometers are designed such that the internal diameter of the open tubular liquid capillary is increased as the desired flow rate is increased. The internal diameter of a capillary for nanovial Electrospray ionisation is typically 1 μm whereas the internal diameter of a capillary for conventional high flow rate Electrospray ionisation may be typically about 130 μm. Experimental techniques have confirmed that the average droplet diameters for nanospray are typically sub-micron whereas for high flow rate Electrospray ionisation the average droplet diameter is between 10-20 μm. If an attempt is made to use a narrow bore capillary at high flow rates then a number of practical problems are encountered. Narrow bore capillaries at high flow rates require greater pressure in order to maintain the required flow rate and are more prone to blockages. Narrow bore capillaries also suffer from poor reproducibility due to the difficulty in producing consistent spraying conditions.
The advent of a new generation of liquid chromatography (LC) columns, such as Ultra Pressure LC (UPLC) and monolithic LC columns, has facilitated high chromatographic efficiency for short retention times with the use of high mobile phase flow rates (500-3000 μl/min). These technologies have reversed the previous trend of reducing both the LC column dimension and the flow rate. As a result, there exists a need for a high efficiency Electrospray ionisation ion source which exhibits reduced matrix suppression effects and which is capable of operating at relatively high flow rates.
It is therefore desired to provide an improved ion source.